{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:33:34Z","timestamp":1770914014812,"version":"3.50.1"},"reference-count":137,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"grant-in-aid for Scientific Research","award":["21K15554"],"award-info":[{"award-number":["21K15554"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Stem cell therapy for ischemic stroke holds great promise for the treatment of neurological impairment and has moved from the laboratory into early clinical trials. The mechanism of action of stem cell therapy includes the bystander effect and cell replacement. The bystander effect plays an important role in the acute to subacute phase, and cell replacement plays an important role in the subacute to chronic phase. Intraarterial (IA) transplantation is less invasive than intraparenchymal transplantation and can provide more cells in the affected brain region than intravenous transplantation. However, transplanted cell migration was reported to be insufficient, and few transplanted cells were retained in the brain for an extended period. Therefore, the bystander effect was considered the main mechanism of action of IA stem cell transplantation. In most clinical trials, IA transplantation was performed during the acute and subacute phases. Although clinical trials of IA transplantation demonstrated safety, they did not demonstrate satisfactory efficacy in improving patient outcomes. To increase efficacy, increased migration of transplanted cells and production of long surviving and effective stem cells would be crucial. Given the lack of knowledge on this subject, we review and summarize the mechanisms of action of transplanted stem cells and recent advancements in preclinical and clinical studies to provide information and guidance for further advancement of acute\/subacute phase IA stem cell transplantation therapy for ischemic stroke.<\/jats:p>","DOI":"10.3390\/bioengineering10010033","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:38:43Z","timestamp":1672205923000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stem Cell Therapy for Acute\/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials"],"prefix":"10.3390","volume":"10","author":[{"given":"Susumu","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"},{"name":"Department of Neurosurgery, Sasebo General Hospital, Nagasaki 857-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiharu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"},{"name":"Department of Neurosurgery, Sasebo General Hospital, Nagasaki 857-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutaka","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-8710","authenticated-orcid":false,"given":"Katsuya","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Occupational Therapy Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuutaka","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-8089","authenticated-orcid":false,"given":"Shunsuke","family":"Ishizaka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6248-0690","authenticated-orcid":false,"given":"Koki","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi","family":"Morofuji","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Hiu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Izumo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-2463","authenticated-orcid":false,"given":"Shigeru","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 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